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The specific inhibition of influenza A virus maturation by amantadine: an electron microscopic examination
R W Ruigrok1, E M Hirst, A J Hay
1National Institute for Medical Research, Mill Hill, London, U.K.
Abstract:
Amantadine specifically inhibits the release of virus particles from cells infected with the Rostock (H7N1) strain of influenza A virus, apparently as a consequence of a membrane protein M2-mediated conversion of haemagglutinin (HA) to its low pH conformation. Electron microscopic observations, together with immunogold labelling, showed that amantadine action does not alter the distribution of HA on the cell surface nor does it prevent the formation of budding virus particles. It was not possible, however, to discern whether low pH HA inhibited the final stage in virus maturation, i.e. pinching off, or simply prevented release of fully formed particles.
Insights
Amantadine, an antiviral drug, stops influenza A virus (H7N1) release by affecting the M2 protein and haemagglutinin conformation. This prevents virus particle release without altering HA distribution or budding.
Area of Science:
- Virology
- Antiviral Drug Research
- Cell Biology
Background:
- Influenza A virus relies on specific proteins for replication and release.
- Amantadine is a known antiviral agent with a mechanism not fully elucidated for all strains.
- The Rostock (H7N1) influenza A strain presents a model for studying viral release mechanisms.
Purpose of the Study:
- To investigate the effect of amantadine on the release of Rostock (H7N1) influenza A virus particles.
- To elucidate the role of the M2 protein and haemagglutinin (HA) conformation in amantadine's antiviral activity.
Main Methods:
- Utilized electron microscopy to observe virus particle formation and release.
- Employed immunogold labelling to track haemagglutinin distribution on infected cell surfaces.
- Studied amantadine's impact on virus-infected cells at the molecular level.
Main Results:
- Amantadine specifically inhibited the release of influenza A virus (H7N1) particles.
- The drug's action appears linked to M2 protein-mediated conversion of HA to its low pH conformation.
- No alteration in HA cell surface distribution or budding virus particle formation was observed.
- The precise stage of inhibition (maturation vs. final release) remained undetermined.
Conclusions:
- Amantadine effectively blocks influenza A virus (H7N1) release, likely by altering HA conformation via the M2 protein.
- The study highlights a specific mechanism of amantadine's antiviral action.
- Further research is needed to pinpoint the exact step in virus maturation inhibited by amantadine.
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